OP-15 - Tocotrienols induce the expression of specific miRNA in breast cancer cells

Abstract

We have demonstrated that γ-and δ-tocotrienol (γ-and δ-T3) induce apoptosis in human breast cancer cells (MDA-MB-231 and MCF-7) at least in part, by the binding and activation of the estrogen receptor-β (ERβ). Further experiments conducted in HeLa cells, a line of human cervical cancer cells void of any canonical ER, demonstrated that γ-and δ-T3 induce Ca2+ release. This event is eventually followed by the induction of specific Ca-dependent signals leading to the expression and activation of IRE1-α and, in turn, to the alternative splicing of the pro-apoptotic protein sXBP-1 and other molecules involved in the Unfolded Protein Response, the core pathway coping with endoplasmic reticulum (EndoR) stress in eukaryotic cells. More recently, we observed that γ-T3 modulates the expression of a specific set of miRNAs in HeLa cells. The list of modulated miRNAs was intersected with the differential gene expression profile of HeLa cells treated with γ-T3 versus untreated cells. On the basis of data interrogation, we focused our attention on miR190b, which is involved in the alternative splicing of the pro-apoptotic protein XBP-1. Experiments based on miR190b silencing confirmed its role in the alternative splicing of XBP1 and in IRE-1 pathway. Our observations suggest that tocotrienols may have a potential role in the clinical management of some specific kind of cancer.